eMedicine Specialties > Physical Medicine and Rehabilitation > Peripheral Neuropathy

Charcot-Marie-Tooth Disease: Treatment & Medication

Author: Divakara Kedlaya, MBBS, Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine
Contributor Information and Disclosures

Updated: Feb 16, 2009

Treatment

Rehabilitation Program

Physical Therapy

Daily heel-cord stretching exercises are desirable to prevent Achilles tendon shortening. Special shoes with good ankle support may be needed. Physical therapy can assist with ambulation and provide necessary evaluation and training with orthoses, such as an ankle-foot orthosis (AFO). Patients often require an AFO to correct foot drop and to aid walking.14

Some patients require the use of forearm crutches or a cane for improved gait stability, but fewer than 5% of patients need wheelchairs. Advise patients with Charcot-Marie-Tooth disease (CMT) about weight management, because obesity makes ambulation more difficult. Encourage exercise within each individual patient's capability. Most patients with CMT usually remain physically active.

Related eMedicine topics:
Foot Drop
Rehabilitation Management of Neuromuscular Disease

Occupational Therapy

An occupational therapist may recommend the use of adaptive equipment for activities of daily living (ADL) and self-care. Fitting of a proper orthosis and keeping the wrist and hand in functional position may be required. Vocational and avocational training regarding the importance of career and employment implications may be needed because of persistent weakness of the hands and/or feet.4,5

Medical Issues/Complications

  • In Charcot-Marie-Tooth disease (CMT), no treatment currently exists to reverse or slow the natural disease process for the underlying disorder. Nothing can correct the abnormal myelin, prevent the myelin's degeneration, or prevent axonal degeneration.
  • Stem-cell and gene-transfer therapies are the most promising forms of treatment for the cure of CMT. Some promising results have been reported for antiprogesterone therapy and ascorbic acid treatment for CMT-1A in animal CMT-1A models. Progesterone-receptor antagonists have reduced PMP-22 overexpression and clinical severity in a CMT-1A rat model. Furthermore, ascorbic acid treatment reduced premature death and demyelination in a CMT-1A mouse model. There is also the prospect of developing drugs to reduce the effects of PMP-22 overexpression in gene duplications by down-regulation via the promoter. Improved understanding of the genetics and biochemistry of the disorder offers hope for an eventual treatment.
  • Patients often are evaluated and managed symptomatically by a team that includes a physiatrist, a neurologist, an orthopedic surgeon, and physical and occupational therapists.

Surgical Intervention

Orthopedic surgery may be required to correct severe pes cavus deformities, scoliosis, and other joint deformities.2,15

Related eMedicine topics:
Neuromuscular Scoliosis
Neuropathic Arthropathy (Charcot Joint)
Pes Cavus

Consultations

Consult a specialist in neurogenetics to order specific genetic tests and proper genetic counseling.

Medication

Avoid drugs and medications known to cause nerve damage (eg, vincristine,16,17 isoniazid, nitrofurantoin). Identify the cause of any pain as accurately as possible. Musculoskeletal pain may respond to acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs). Neuropathic pain may respond to tricyclic antidepressants or antiepileptic drugs, such as carbamazepine or gabapentin.

Dyck and colleagues18 and Ginsberg and coauthors19 described a few individuals with Charcot-Marie-Tooth disease type 1 (CMT-1) and sudden deterioration in whom treatment with steroids (prednisone) or intravenous immunoglobulin produced variable levels of improvement. Sahenk and colleagues have been studying the effects of neurotrophin-3 on individuals with CMT-1A. Passage and coauthors20 reported therapeutic benefits from the administration of ascorbic acid (vitamin C) in a mouse model of CMT-1.

Nonsteroidal anti-inflammatory drugs

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase (COX) activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.


Ibuprofen (Motrin, Ibuprin)

DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Adult

200-400 mg PO q4-6h while symptoms persist; not to exceed 3.2 g/d

Pediatric

<6 months: Not established
6 months to 12 years: 4-10 mg/kg/dose PO tid/qid
>12 years: Administer as in adults

Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity; peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy


Naproxen (Naprelan, Naprosyn, Anaprox)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which results in a decrease in prostaglandin synthesis.

Adult

500 mg PO followed by 250 mg q6-8h; not to exceed 1.25 g/d

Pediatric

<2 years: Not established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d

Coadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug

Cyclooxygenase-2 inhibitors

Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is clearly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.


Celecoxib (Celebrex)

Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek lowest dose of celecoxib for each patient.

Adult

200 mg/d PO qd; alternatively, 100 mg PO bid

Pediatric

Not established

Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration of celecoxib with rifampin may decrease celecoxib plasma concentrations

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, conditions predisposing to fluid retention; severe heart failure and hyponatremia, because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate symptoms and signs suggesting liver dysfunction or in cases of abnormal liver lab results

Analgesics

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties, which are beneficial for patients who experience pain.


Acetaminophen (Tylenol)

DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.

Adult

325-650 mg PO q4-6h or 1000 mg tid/qid; not to exceed 4 g/d

Pediatric

<12 years: 10-15 mg/kg/dose PO q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO q4h; not to exceed 5 doses in 24 h

Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity

Documented hypersensitivity; known G-6-P deficiency

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; APAP is contained in many OTC products and combined use with these products may result in cumulative APAP doses exceeding recommended maximum dose

Tricyclic antidepressants

A complex group of drugs that has central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission, blocking the active reuptake of norepinephrine and serotonin.


Amitriptyline (Elavil)

Analgesic for certain chronic and neuropathic pain. Inhibits membrane pump responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neuron.

Adult

30-100 mg/d PO qhs

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase levels; inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram

Documented hypersensitivity; patient has taken MAO inhibitors in past 14 d; has history of seizures, cardiac arrhythmias, glaucoma, and urinary retention

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; avoid using in elderly patients


Nortriptyline (Pamelor)

Has demonstrated effectiveness in the treatment of chronic pain. By inhibiting the reuptake of serotonin and/or norepinephrine by the presynaptic neuronal membrane, this drug increases the synaptic concentration of these neurotransmitters in the central nervous system.
Pharmacodynamic effects, such as the desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors, also appear to play a role in its mechanisms of action.

Adult

25 mg PO tid/qid, up to 150 mg/d

Pediatric

<12 years: Not established
>12 years:
25-35 kg: 10-20 mg/d PO
35-54 kg: 25-35 mg/d PO

Cimetidine may increase nortriptyline levels when used concurrently; nortriptyline may increase prothrombin time in patients stabilized with warfarin

Documented hypersensitivity; narrow-angle glaucoma; do not administer to patients who have taken MAO inhibitors in past 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; due to pronounced effects in cardiovascular system, best to avoid in elderly patients


Doxepin (Sinequan)

Inhibits histamine and acetylcholine activity and has proven useful in treatment of various forms of depression associated with chronic and neuropathic pain.

Adult

10-150 mg/d PO hs or divided bid/tid

Pediatric

<12 years: Not recommended
>12 years: 25-50 mg/d PO hs or bid/tid and increase gradually to 100 mg/d

Decreases antihypertensive effects of clonidine but increases effects of sympathomimetics and benzodiazepines; effects of desipramine increase with phenytoin, carbamazepine, and barbiturates

Documented hypersensitivity; urinary retention; acute recovery phase following myocardial infarction; glaucoma

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and patients receiving thyroid replacement


Desipramine (Norpramin)

May increase synaptic concentration of norepinephrine in CNS by inhibiting reuptake by presynaptic neuronal membrane. May have effects in the desensitization of adenyl cyclase, down-regulation of beta-adrenergic receptors, and down-regulation or serotonin receptors.

Adult

75 mg/d PO initially in equally divided doses and increase gradually prn; not to exceed 300 mg/d
Elderly patients: 25-100 mg/d PO; not to exceed 150 mg/d

Pediatric

<6 years: Not established
6-12 years: 1-5 mg/kg/d PO in equally divided doses; not to exceed 5 mg/kg qd
>12 years: 25-50 mg/d PO, initially and increase gradually to 100 mg/d prn; not to exceed 150 mg/d; give in single or equally divided doses

Decreases antihypertensive effects of clonidine but increases effects of sympathomimetics and benzodiazepines; effects of desipramine increase with phenytoin, carbamazepine, and barbiturates

Documented hypersensitivity; narrow-angle glaucoma, recent postmyocardial infarction; patients currently receiving MAO inhibitors or fluoxetine or who have taken them in the previous 2 wk

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, and patients receiving thyroid replacement

Anticonvulsants

Used to manage pain and provide sedation in neuropathic pain.


Gabapentin (Neurontin)

Membrane stabilizer, a structural analogue of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 subunit of the calcium channel.

Adult

300-3600 mg PO in 3-4 divided doses

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Antacids may significantly reduce bioavailability of gabapentin (administer at least 2 h following antacids); may increase norethindrone levels significantly

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in patients with renal insufficiency
If creatinine clearance is 30-60 mL/min, dose should be 300 mg bid; if 15-30 mL/min, 300 mg qd; if <15 mL/min, 300 mg qod; in hemodialysis patients, administer 200-300 mg after each dialysis

More on Charcot-Marie-Tooth Disease

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Multimedia: Charcot-Marie-Tooth Disease
References
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Further Reading

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Keywords

Charcot-Marie-Tooth disease, Charcot Marie Tooth, Charcot Marie Tooth disease, neuropathy, Charcot, Charcot Marie, pes cavus, connexin, Charcot Marie Tooth syndrome, hereditary motor sensory neuropathy, HMSN, peroneal muscular atrophy, PMA, CMT

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Contributor Information and Disclosures

Author

Divakara Kedlaya, MBBS, Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine
Divakara Kedlaya, MBBS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, and Colorado Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Milton J Klein, DO, MBA, Consulting Physiatrist, Sewickley Valley Hospital, Allegheny General Hospital, Harmarville Rehabilitation Center, Ohio Valley General Hospital, and Aliquippa Community Hospital
Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Michael T Andary, MD, MS, Residency Program Director, Professor, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine
Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, and Association of Academic Physiatrists
Disclosure: allergan Honoraria Speaking and teaching

CME Editor

Kelly L Allen, MD, Regional Medical Director, IMX-Medical Management Services
Disclosure: Nothing to disclose.

Chief Editor

Robert H Meier III, MD, Director, Amputee Services of America; Active Medical Staff, Presbyterian/St Luke's Hospital, Spalding Rehabilitation Hospital, Select Specialty Hospital; Consulting Staff, Kindred Hospital
Robert H Meier III, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation and Association of Academic Physiatrists
Disclosure: Nothing to disclose.

 
 
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